CS 177 Introduction to Bioinformatics Fall 2005

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CS 177 Introduction to BioinformaticsFall 2005

• Instructor Anna Panchenko (hcnap2003_at_yahoo.com)
• Instructor Tom Madej (tom_ncbi_at_yahoo.com)

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• Lecture 1 Introduction
• Instructors
• Course goals
• Grading policy
• Motivating problem
• Course overview
• Molecular basis of cellular processes
• Historical timeline

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Course Goals

• The student will be introduced to the fundamental
  problems and methods of bioinformatics.
• The student will become thoroughly familiar with
  on-line public bioinformatics databases and their
  available software tools.
• The student will acquire a background knowledge
  of biological systems so as to be able to
  interpret the results of database searches, etc.
• The student will also acquire a general
  understanding of how important bioinformatics
  algorithms/software tools work, and how the
  databases are organized.

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Grading Policy

• Homework 50, weekly assignments
• Mid-term exam 20
• Final exam 30

All examinations, papers, and other graded work
products and assignments are to be completed in
conformance with The George Washington
University Code of Academic Integrity.
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Important!

• Please get computer accounts for Tompkins 405 by
  filling out a form in the TA room on the 4th
  floor of Tompkins.
• Office hours AP available before class, TM
  available after class. If you want to see AP or
  TM before class, please ask in advance.
• We will also accept questions by email, although
  we may not be able to reply immediately.

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Homework

• Homework assignments are due by the start of the
  next class period (330 pm Monday).
• For an assignment turned in up to one week late
  20 penalty.
• Homework more than one week late No credit!
• Assignments/exams are to be done individually, no
  copying of assignments is allowed!

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NCBI Books

• NCBI home page http//www.ncbi.nlm.nih.gov
• Follow the Books link.
• 45 books available (currently).
• Many specialty topics.
• Also useful general references.
• Searchable!
• Exercise search the books with phylogenetic
  tree.

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What is Bioinformatics?

• A merger of biology, computer science, and
  information technology.
• Enables the discovery of new biological insights
  and unifying principles.
• Born from necessity, because of the massive
  amount of information required to describe
  biological organisms and processes.

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Severe Acute Respiratory Syndrome (SARS)

• SARS is a respiratory illness caused by a
  previously unrecognized coronavirus first
  appeared in Southern China in Nov. 2002.
• Between Nov. 2002 and July 2003, there were 8,098
  cases worldwide and 774 fatalities (WHO).
• The global outbreak was over by late July 2003.
  A few new cases have arisen sporadically since
  then in China.
• There is currently no vaccine or cure available.

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Fig. 2 from Rota et al.
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Phylogenetic analysis of coronavirus proteins
Fig. 2 from Rota et al.
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Conserved motifs in coronavirus S proteins.
Fig. 2 from Rota et al.
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• Exercise!
• Look up the SARS genome on the NCBI website
  www.ncbi.nlm.nih.gov
• Notice that you get 2 hits on the Genome
  database!

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The (ever expanding) Entrez System
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NCBI Databases

• Databases are indexed for quick and efficient
  searching.
• Databases are cross-linked to each other.

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Exercise!

• Search the Entrez Protein database with the
  keyword interleukin.
• Follow the link, then look at the different
  report formats.
• Also try a search of Protein with interleukin
  AND human orgn.

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Course Overview

• Lecture 1 Introduction
• Instructors
• Grading policy
• Motivating problem
• Course overview
• Molecular basis of cellular processes
• Historical timeline

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• Lecture 2 General principles of DNA/RNA
  structure and stability
• Physico-chemical properties of nucleic acids
• RNA folding and structure prediction
• Gene identification
• Genome analysis

• Lecture 3 General principles of protein
  structure and stability
• Physico-chemical properties of proteins
• Prediction of protein secondary structure
• Protein domains and prediction of domain
  boundaries
• Protein structure-function relationships

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• Lecture 4 Sequence alignment algorithms
• The alignment problem
• Pairwise sequence alignment algorithms
• Multiple sequence alignment algorithms
• Sequence profiles and profile alignment methods
• Alignment statistics

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• Lecture 5 Computational aspects of protein
  structure, part I
• Protein folding problem
• Problem of protein structure prediction
• Homology modeling
• Protein design
• Prediction of functionally important sites

• Lecture 6 Computational aspects of protein
  structure, part II
• Structure-structure alignment algorithms
• Significance of structure-structure similarity
• Protein structure classification

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• Lecture 7 Bioinformatics databases
• Sequence and sequence alignment formats, data
  exchange
• Public sequence databases
• Sequence retrieval and examples
• Public protein structure databases
• Lab exercises

• Lecture 8 Bioinformatics database search tools
• Sequence database search tools
• Structure database search tools
• Assessment of results, ROC analysis
• Lab exercises

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• Lecture 9 Phylogenetic analysis, part I
• Molecular basis of evolution
• Taxonomy and phylogenetics
• Phylogenetic trees and phylogenetic inference
• Software tools for phylogenetic analysis

• Lecture 10 Phylogenetic analysis, part II
• Accuracies and statistical tests of phylogenetic
  trees
• Genome comparisons
• Protein structure evolution

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• Lecture 11 Experimental techniques for
  macromolecular analysis
• Sequencing, PCR
• Protein crystallography
• Mass spectroscopy
• Microarrays
• RNA interference

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• Lecture 12 Systems biology
• Genomic circuits
• Modeling complex integrated circuits
• Protein-protein interaction
• Metabolic networks

Lecture 13 Review
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Molecular Biology Background

• Cells general structure/organization
• Molecules that make up cells
• Cellular processes what makes the cell alive

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Two Cell Organizations

• Prokaryotes lack nucleus, simpler internal
  structure, generally quite smaller
• Eukaryotes with nucleus (containing DNA) and
  various organelles

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Selected organelles

• Nucleus contains chromosomes/DNA
• Mitochondria generate energy for the cell,
  contains mitochrondrial DNA
• Ribosomes where translation from mRNA to
  proteins take place (protein synthesis machinery)
• Lysosomes where protein degradation takes place

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Cells can become specialized
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Three domains of life

• Prokarya
• Bacteria
• Archaea
• Eukarya
• Eukaryotes

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Universal phylogenetic tree.
Fig. 1 from N.R. Pace, Science 276 (1997)
734-740.
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Molecules in the cell

• Proteins catalyze reactions, form structures,
  control membrane permeability, cell signaling,
  recognize/bind other molecules, control gene
  function
• Nucleic acids DNA and RNA encode information
  about proteins
• Lipids make up biomembranes
• Carbohydrates energy sources, energy storage,
  constituents of nucleic acids and surface
  membranes
• Other small molecules e.g. ATP, water, ions,
  etc.

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• Exercise!
• Retrieve a protein structure from the SARS
  coronavirus from the NCBI website you can use
  www.ncbi.nlm.nih.gov/Structure/
• Look at the structure for the SARS protease
  using Cn3D.

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The Central Dogma of Molecular Biology
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Timeline

• 1859 Darwin publishes On the Origin of Species
• 1865 Mendels experiments with peas show that
  hereditary traits are passed on to offspring in
  discrete units.
• 1869 Meischer isolates DNA.
• 1895 Rontgen discovers X-rays.
• 1902 Sutton proposes the chromosome theory of
  heredity.

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Timeline (cont.)

• 1911 Morgan and co-workers establish the
  chromosome theory of heredity, working with fruit
  flies.
• 1943 Astbury observes the first X-ray pattern of
  DNA.
• 1944 Avery, MacLeod, and McCarty show that DNA
  transmits heritable traits (not proteins!).
• 1951 Pauling and Corey predict the structure of
  the alpha-helix and beta-sheet.

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Timeline (cont.)

• 1953 Watson and Crick propose the double helix
  model for DNA based on X-ray data from Franklin
  and Wilkins.
• 1955 Sanger announces the sequence of the first
  protein to be analyzed, bovine insulin.
• 1955 Kornberg and co-workers isolate the enzyme
  DNA polymerase (used for copying DNA, e.g. in
  PCR).
• 1958 The first integrated circuit is constructed
  by Kilby at Texas Instruments.

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Timeline (cont.)

• 1960 Perutz and Kendrew obtain the first X-ray
  structures of proteins (hemoglobin and
  myoglobin).
• 1961 Brenner, Jacob, and Meselson discover that
  mRNA transmits the information from the DNA in
  the nucleus to the cytoplasm.
• 1965 Dayhoff starts the Atlas of Protein Sequence
  and Structure.
• 1966 Nirenberg, Khorana, Ochoa and colleagues
  crack the genetic code!
• 1970 The Needleman-Wunsch algorithm for sequence
  comparison is published.

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Timeline (cont.)

• 1972 Dayhoff develops the Protein Sequence
  Database (PSD).
• 1972 Berg and colleagues create the first
  recombinant DNA molecule.
• 1973 Cohen invents DNA cloning.
• 1975 Sanger and others (Maxam, Gilbert) invent
  rapid DNA sequencing methods.

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Timeline (cont.)

• 1980 The first complete gene sequence for an
  organism (Bacteriophage FX174) is published. The
  genome consists of 5,386 bases coding 9 proteins.
• 1981 The Smith-Waterman algorithm for sequence
  alignment is published.
• 1981 IBM introduces its Personal Computer to the
  market.
• 1982 The GenBank sequence database is created at
  Los Alamos National Laboratory.

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Timeline (cont.)

• 1983 Mullis and co-workers describe the PCR
  reaction.
• 1985 The FASTP algorithm is published by Lipman
  and Pearson.
• 1986 The SWISS-PROT database is created.
• 1986 The Human Genome Initiative is announced by
  DOE.
• 1988 The National Center for Biotechnology
  Information (NCBI) is established at the National
  Library of Medicine in Bethesda.

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Timeline (cont.)

• 1992 Human Genome Systems, in Gaithersburg, MD,
  is founded by Haseltine.
• 1992 The Institute for Genomic Research (TIGR) is
  established by Venter in Rockville, MD.
• 1995 The Haemophilus influenzea genome is
  sequenced (1.8 Mb).
• 1996 Affymetrix produces the first commercial DNA
  chips.

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Timeline (cont.)

• 1988 The FASTA algorithm for sequence comparison
  is published by Pearson and Lipman.
• 1990 Official launch of the Human Genome Project.
• 1990 The BLAST program by Altschul et al., is
  published.
• 1991 The CERN research institute in Geneva
  announces the creation of the protocols which
  make up the World Wide Web.

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Timeline (cont.)

• 1996 The yeast genome is sequenced the first
  complete eukaryotic genome.
• 1996 Human DNA sequencing begins.
• 1997 The E. coli genome is sequenced (4.6 Mb,
  approx. 4k genes).
• 1998 The C. elegans genome is sequenced (97 Mb,
  approx. 20k genes) the first genome of a
  multicellular organism.

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Timeline (cont.)

• 1998 Venter founds Celera in Rockville, MD.
• 1998 The Swiss Institute of Bioinformatics is
  established in Geneva.
• 1999 The HGP completes the first human chromosome
  (no. 22).
• 2000 The Drosophila genome is completed.

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Timeline (cont.)

• 2000 Human chromosome no. 21 is completed.
• 2001 A draft of the entire human genome (3,000
  Mb) is published.
• 2003 The Human Genome is completed! Approx.
  30,000 genes (estimated).

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